Tramutola A, Lanzillotta C, Perluigi M, Butterfield D Allan
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
Brain Res Bull. 2017 Jul;133:88-96. doi: 10.1016/j.brainresbull.2016.06.005. Epub 2016 Jun 15.
Alzheimer disease (AD) is a progressive neurodegenerative disease that affects the elderly population with complex etiology. Many hypotheses have been proposed to explain different causes of AD, but the exact mechanisms remain unclear. In this review, we focus attention on the oxidative-stress hypothesis of neurodegeneration and we discuss redox proteomics approaches to analyze post-mortem human brain from AD brain. Collectively, these studies have provided valuable insights into the molecular mechanisms involved both in the pathogenesis and progression of AD, demonstrating the impairment of numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and degradative systems. Each of these cellular functions normally contributes to maintain healthy neuronal homeostasis, so the deregulation of one or more of these functions could contribute to the pathology and clinical presentation of AD. In particular, we discuss the evidence demonstrating the oxidation/dysfunction of a number of enzymes specifically involved in energy metabolism that support the view that reduced glucose metabolism and loss of ATP are crucial events triggering neurodegeneration and progression of AD.
阿尔茨海默病（AD）是一种渐进性神经退行性疾病，影响老年人群，病因复杂。人们提出了许多假说以解释AD的不同病因，但确切机制仍不清楚。在本综述中，我们将注意力集中在神经退行性变的氧化应激假说上，并讨论氧化还原蛋白质组学方法，以分析来自AD患者脑的尸检人脑组织。总体而言，这些研究为AD发病机制和进展所涉及的分子机制提供了有价值的见解，证明了许多细胞过程受到损害，如能量产生、细胞结构、信号转导、突触功能、线粒体功能、细胞周期进程和降解系统。这些细胞功能中的每一项通常都有助于维持健康的神经元内环境稳定，因此其中一项或多项功能的失调可能导致AD的病理和临床表现。特别是，我们讨论了一些证据，这些证据表明参与能量代谢的多种酶发生氧化/功能障碍，支持了以下观点：葡萄糖代谢降低和ATP丧失是引发神经退行性变和AD进展的关键事件。
